公开(公告)号：US09139645B2

公开(公告)日：2015-09-22

申请号：US13938141

申请日：2013-07-09

Applicant: AMGEN INC.

Inventor： Hosung Min ,  Hailing Hsu ,  Fei Xiong

IPC: C07K7/08 ,  C07K14/00 ,  C07K16/24 ,  C07K1/04 ,  C07K14/47 ,  C07K14/715 ,  C12N15/10 ,  C40B40/02 ,  A61K38/00

CPC classification number: C07K7/08 ,  A61K38/00 ,  A61K38/10 ,  C07K1/047 ,  C07K14/001 ,  C07K14/4702 ,  C07K14/7151 ,  C07K16/241 ,  C07K2319/30 ,  C07K2319/74 ,  C12N15/1037 ,  C40B40/02

Abstract: The present invention concerns therapeutic agents that modulate the activity of TALL-1. In accordance with the present invention, modulators of TALL-1 may comprise an amino acid sequence Dz2Lz4 wherein z2 is an amino acid residue and z4 is threonyl or isoleucyl. Exemplary molecules comprise a sequence of the formulae (SEQ. ID. NO: 100) a1a2a3CDa6La8a9a10Ca12a13a14, (SEQ. ID. NO: 104) b1b2b3Cb5b6Db8Lb10b11b12b13b14Cb16b17b18 (SEQ. ID. NO: 105) c1c2c3Cc5Dc7Lc9c10c11c12c13c14Cc16c17c18 (SEQ. ID. NO: 106) d1d2d3Cd5d6d7WDd10Ld13d14d15Ld16d17d18 (SEQ. ID. NO: 107) e1e2e3Ce5e6e7De9Le11Ke13Ce15e16e17e18 (SEQ. ID NO: 109) f1f2f3Kf5Df7Lf9f10Qf12f13f14 wherein the substituents are as defined in the specification. The invention further comprises compositions of matter of the formula (X1)a—V1—(X2)b wherein V1 is a vehicle that is covalently attached to one or more of the above TALL-1 modulating compositions of matter. The vehicle and the TALL-1 modulating composition of matter may be linked through the N- or C-terminus of the TALL-1 modulating portion. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain.

Abstract translation: 本发明涉及调节TALL-1活性的治疗剂。 根据本发明，TALL-1的调节剂可以包含氨基酸序列Dz2Lz4，其中z2是氨基酸残基，z4是苏氨酰基或异亮氨酰基。 示例性分子包括下式的一个序列（SEQ。ID NO：100）a1a2a3CDa6La8a9a10Ca12a13a14，（SEQ ID NO：104）b1b2b3Cb5b6Db8Lb10b11b12b13b14Cb16b17b18（SEQ ID。NO：105）c1c2c3Cc5Dc7Lc9c10c11c12c13c14Cc16c17c18（SEQ ID。NO：106）d1d2d3Cd5d6d7WDd10Ld13d14d15Ld16d17d18（ SEQ ID NO：107）e1e2e3Ce5e6e7De9Le11Ke13Ce15e16e17e18（SEQ ID NO：109）f1f2f3Kf5Df7Lf9f10Qf12f13f14其中取代基如说明书中所定义。 本发明还包括式（X1）a-V1-（X2）b的物质的组合物，其中V1是共价连接到一种或多种上述TALL-1调节组合物的载体。 载体和TALL-1调节组合物可以通过TALL-1调节部分的N末端或C末端连接。 优选的载体是Fc结构域，优选的Fc结构域是IgG Fc结构域。

公开(公告)号：US11266744B2

公开(公告)日：2022-03-08

申请号：US16206899

申请日：2018-11-30

Applicant: AMGEN INC.

Inventor： Colin V. Gegg ,  Kenneth W. Walker ,  Leslie P. Miranda ,  Fei Xiong

IPC: C07H21/02 ,  C07H21/04 ,  C12P21/06 ,  C12N1/20 ,  C12N15/00 ,  C12N5/00 ,  C07K16/00 ,  A61K47/68 ,  A61K47/60 ,  A61K38/02 ,  C07K17/00

Abstract: Disclosed is a process for preparing a pharmacologically active compound, in which at least one internal conjugation site of an Fc domain sequence is selected that is amenable to conjugation of an additional functional moiety by a defined conjugation chemistry through the side chain of an amino acid residue at the conjugation site. An appropriate amino acid residue for conjugation may be present in a native Fc domain at the conjugation site or may be added by insertion (i.e., between amino acids in the native Fc domain) or by replacement (i.e., removing amino acids and substituting different amino acids). In the latter case, the number of amino acids added need not correspond to the number of amino acids removed from the previously existing Fc domain. This technology may be used to produce useful compositions of matter and pharmaceutical compositions containing them. A DNA encoding the inventive composition of matter, an expression vector containing the DNA, and a host cell containing the expression vector are also disclosed.

公开(公告)号：US10188740B2

公开(公告)日：2019-01-29

申请号：US14796502

申请日：2015-07-10

Applicant: AMGEN INC.

Inventor： Colin V. Gegg ,  Kenneth W. Walker ,  Leslie P. Miranda ,  Fei Xiong

IPC: A61K39/395 ,  A61K47/48 ,  A61K38/02 ,  C07K16/00 ,  C07K17/00 ,  A61K47/60 ,  A61K47/68

Abstract: Disclosed is a process for preparing a pharmacologically active compound, in which at least one internal conjugation site of an Fc domain sequence is selected that is amenable to conjugation of an additional functional moiety by a defined conjugation chemistry through the side chain of an amino acid residue at the conjugation site. An appropriate amino acid residue for conjugation may be present in a native Fc domain at the conjugation site or may be added by insertion (i.e., between amino acids in the native Fc domain) or by replacement (i.e., removing amino acids and substituting different amino acids). In the latter case, the number of amino acids added need not correspond to the number of amino acids removed from the previously existing Fc domain. This technology may be used to produce useful compositions of matter and pharmaceutical compositions containing them. A DNA encoding the inventive composition of matter, an expression vector containing the DNA, and a host cell containing the expression vector are also disclosed.